Nat. Rev. Neurol. doi: /nrneurol

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Nat. Rev. Neurol. doi:10.1038/nrneurol.2017.117 Figure 1 Conceptual models, causes and consequences of fatigue in neurological disease Figure 1 | Conceptual models, causes and consequences of fatigue in neurological disease. The relationships between factors that contribute to fatigue are complex and highly interdependent. Performance fatigability on motor exercises or cognitive tests can result from peripheral factors, including loss of muscle force in the context of myopathies and myasthenia gravis, or central factors, including brain atrophy and altered functional connectivity in the context of multiple sclerosis (MS), stroke and other CNS conditions. Self-perceived fatigue, scored using standardized questionnaires, can result from hypothalamic dysfunction and impaired central regulation of physical activity (which is dependent on energetic and neural feedback) as well as medications, poor sleep, and psychological factors such as mood, motivation, and depression — which are themselves risk factors for fatigue. Laboratory and diagnostic evaluations, such as structural and functional neuroimaging studies, EEG, electromyography, and metabolic and hormonal or neuroendocrine measurements can help to identify potential causes of fatigue. HPA, hypothalamic–pituitary–adrenal. Penner, I.-K. & Paul, F. (2017) Fatigue as a symptom or comorbidity of neurological diseases Nat. Rev. Neurol. doi:10.1038/nrneurol.2017.117